Postmortem genetic tests to complete modern autopsies

In seven out of ten cases, genetic tests on the dead could unveil the likely cause of death.

Each year, 11,000 people under the age of 45 die suddenly and unexpectedly of natural causes in the United States. If the cause of death isn’t determined, it leaves living relatives with an incomplete family health history, and at risk. Using genetic testing in autopsies may be one way to resolve the uncertainty. Ali Torkamani, Director of Genome Informatics and Drug Discovery at The Scripps Translational Science Institute explored the potential of “molecular autopsies” in his latest study.

ResearchGate: Why is it important to know the cause of death?

Ali Torkamani: Knowing the cause of death can inform whether living relatives are at risk. Many of the causes of sudden death can either be monitored or, in some cases, a direct intervention is possible. Knowing whether a living relative is at risk can reduce their risk of succumbing to the same fate.

RG: Have genetic tests played a role in autopsies in the past?

Torkamani: Yes, but not in a systematic manner. There is certainly a subset of medical examiners that utilize genetic testing in their practice, but it tends to be of limited scope - generally just testing for suspected arrhythmias. Recent surveys have shown that the majority of medical examiners have never ordered a genetic test. The primary reason for this appears to be the cost.

RG: The rate of autopsies has declined from 50 percent to 10 percent in 2008. Why do you think that is?

Torkamani: The reasons most commonly cited for a decline in the rate of clinical autopsies are: firstly, lack of reimbursement or financial support for clinical autopsies, and secondly, reluctance for living relatives to consent to an invasive procedure.

RG: Is postmortem genetic testing different to genetic testing in the living?

Torkamani: Fundamentally, no. The technical procedures involved are largely the same. In postmortem genetic testing you can do certain things that are not possible in genetic testing of the living, for example testing for somatic mosaicism in the heart tissue of the deceased.

RG: How did you study postmortem genetic testing?

Torkamani: We worked with the San Diego medical examiner to recruit cases of sudden death in individuals under 45 years of age. For cases that qualified, we performed exome sequencing on the deceased and their family where possible.

RG: What were your results?

Torkamani: 25 cases were sequenced, with nine including both parents of the deceased. Clinical autopsies discovered the likely cause of death in five cases. A likely cause of death was identified by molecular autopsy in four cases (16 percent), a plausible cause in six (24 percent), and a speculative cause in seven (28 percent); no mutations were identified in eight (32 percent). The likely genetic cause of death was corroborated with clinical autopsy findings in two of five cases. All other clinical autopsy findings (three cases) could be linked to a plausible or speculative genetic cause. Seventy percent (7/10 cases) of likely and plausible pathogenic mutations were inherited from relatives who did not die suddenly.

RG: Which role do you see postmortem genetic tests play in the future?

Torkamani: As the cost of sequencing continues to decline, I suspect postmortem genetic testing will become more and more prevalent. It will likely start with suspected cases of arrhythmia and other cardiovascular conditions. I believe the benefits to living relatives would support the case.